A single center experience with high-dose (HD) IL-2 treatment for patients with advanced melanoma and pilot investigation of a novel gene expression signature as a predictor of response

Abstract

9003 Background: HD IL-2 remains one of two FDA-approved therapies for the treatment of patients (pts) with advanced melanoma. Initial studies conducted 15–20 years ago reported 16% response rate with 8% of pts achieving durable responses. The toxicity of HD IL-2 limits its application to pts treated in specialized centers. We present the clinical outcome of pts treated over a recent 2 year period with HD IL-2 at a single institution and an associated retrospective pilot study evaluating the predictive value of a novel tumor gene expression signature. Methods: Clinical and radiological data were collected and analyzed on 49 consecutive pts treated with HD IL-2 at Beth Israel Deaconess Medical Center from 10/05 - 10/07. Response was evaluated via RECIST. Formalin-fixed paraffin embedded tumor was obtained on consenting pts and classified as either Class 1, defined by melanocyte-specific genes including MITF, or Class 2, represented by immune genes, using the DNA-mediated Annealing, Selection, and Ligation (DASL) technique. Two-sided Fisher's Exact test was used to compare the proportion of responses for pts in the two classes. Results: Clinical response occurred in 16 of the 49 pts (32.6%), with 5 pts (10.2%) having a CR. Two other pts had stable disease > 12 mos; 3 pts who progressed after response had resection to NED. 10 pts remain disease/progression free at a minimum of 16 mos following treatment. 28 pts (including 13 of 16 responders) had sufficient tumor for DASL analysis. Among the 21 categorized as Class 1, 7 (33%) were responders. Of the 7 classified as Class 2, 6 (86%) were responders. This difference in response was statistically significant (p = 0.0286). Conclusions: The overall and CR rates in a contemporary series of pts with metastatic melanoma treated with HD IL-2 are twice that reported in initial studies suggesting some treatment selection on clinical grounds since the 1990s. Pts with tumors expressing an immune signature by DASL appeared more likely to respond. This finding requires prospective validation, but suggests immune-related gene expression might contribute to IL-2 responsiveness. [Table: see text]